Skip to main content
SpringerLink
Log in

Introduction to Calreticulin

  • Chapter
Calreticulin

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

Over 30 years ago calreticulin, then known as the high affinity calcium binding protein (HACBP), was identified and purified from isolated skeletal muscle sarcoplasmic reticulum vesicles.1,2 Surprisingly, it took almost 20 years to realize that the protein is a major component of the endoplasmic reticulum (ER) in non-muscle cells3. However, today, calreticulin is considered one of the best markers for the ER. In 1989 isolation of cDNA encoding calreticulin was reported3,4 and provided a useful tool to carry out biochemical, molecular biological and cell biological studies of the protein. This led to a number of advances on the structure and function of calreticulin. The recent application of calreticulin gene deletion in mice,5,6 C. elegans 7,8 and in Dictyostelium 9 have led to exciting discoveries of the role of calreticulin in organogenesis and several pathologies. Moreover, long awaited structural studies on calreticulin10 and calnexin11 provided the first insights into 3D structure of ER luminal proteins and their domains. This will have a tremendous impact on the future studies on these and other ER chaperones.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ostwald TJ, MacLennan DH. Isolation of a high affinity calcium-binding protein from sarcoplasmic reticulum. J Biol Chem 1974; 249:974–79.

    PubMed  CAS  Google Scholar 

  2. Ostwald TJ, MacLennan DH, Dorrington KJ. Effects of cation binding on the conformation of calsequestrin and the high affinity calcium-binding protein of sarcoplasmic reticulum. J Biol Chem 1974; 249:5867–71.

    PubMed  CAS  Google Scholar 

  3. Fliegel L, Burns K, MacLennan DH et al. Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 1989; 264:21522–28.

    PubMed  CAS  Google Scholar 

  4. Smith MJ, Koch GLE. Multiple zones in the sequence of calreticulin (CRP55, calregulin, HACBP), a major calcium binding ER/SR protein. EMBO J 1989; 8:3581–86.

    PubMed  CAS  Google Scholar 

  5. Mesaeli N, Nakamura K, Zvaritch E et al. Calreticulin is essential for cardiac development. J Cell Biol 1999; 144:857–68.

    Article  PubMed  CAS  Google Scholar 

  6. Rauch F, Prud’homme J, Arabian A et al. Heart, brain, and body wall defects in mice lacking calreticulin. Exp Cell Res 2000; 256:105–11.

    Article  PubMed  CAS  Google Scholar 

  7. Park BJ, Lee DG, Yu JR et al. Calreticulin, a calcium-binding molecular chaperone, is required for stress response and fertility in Caenorhabditis elegans. Mol Biol Cell 2001; 12:2835–45.

    PubMed  CAS  Google Scholar 

  8. Xu K, Tavernarakis N, Driscoll M. Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca2+ release from the endoplasmic reticulum. Neuron 2001; 31:957–71.

    Article  PubMed  CAS  Google Scholar 

  9. Muller-Taubenberger A, Lupas AN, Li H et al. Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis. EMBO J 2001; 20:6772–82.

    Article  PubMed  CAS  Google Scholar 

  10. Ellgaard L, Riek R, Herrmann T et al. NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA 2001; 98:3133–38.

    Article  PubMed  CAS  Google Scholar 

  11. Schrag JD, Bergeron JJM, Li Y et al. The structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol Cell 2001; 8:633–44.

    Article  PubMed  CAS  Google Scholar 

  12. Michalak M. Calreticulin. Austin: Landes Bioscience, 1996.

    Google Scholar 

  13. Meldolesi J, Krause K-H, Michalak M. Calreticulin: how many functions in how many cellular compartments? Como, April 1996. Cell Calcium 1996; 20:83–86.

    Article  PubMed  CAS  Google Scholar 

  14. Michalak M, Mariani P, Opas M. Calreticulin, a multifunctional Ca2+ binding chaperone of the endoplasmic reticulum. Biochem Cell Biol 1998; 76:779–85.

    PubMed  CAS  Google Scholar 

  15. Llewellyn DH, Johnson S, Eggleton P. Calreticulin comes of age. Trends Cell Biol 2000; 10:399–402.

    Article  PubMed  CAS  Google Scholar 

  16. Krause K-H, Michalak M. Calreticulin. Cell 1997; 88:439–43.

    Article  PubMed  CAS  Google Scholar 

  17. Khanna NC, Waisman DM. Development of a radioimmunoassay for qualification of calregulin in bovine tissues. Biochemistry 1986; 25:1078–82.

    Article  PubMed  CAS  Google Scholar 

  18. Waisman DM, Khanna NC, Tokuda M. Identification of a major bovine heart Ca2+ binding protein. Biochem. Biophys Res Commun 1986; 139:596–603.

    Article  CAS  Google Scholar 

  19. Tokuda M, Khanna NC, Waisman DM. Identification of bovine brain calcium binding proteins. Cell Calcium 1987; 8:229–39.

    Article  PubMed  CAS  Google Scholar 

  20. Khanna NC, Tokuda M, Waisman DM. Comparison of cairegulins from vertebrate livers. Biochcm J 1987; 242:245–51.

    CAS  Google Scholar 

  21. Khanna NC, Tokuda M, Waisman DM. Calregulm: purification, cellular localization, and tissue distribution. Meth Enzymol 1987; 139:36–50.

    Article  PubMed  CAS  Google Scholar 

  22. Baksh S, Michalak M. Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. J Biol Chem 1991; 266:21458–65.

    PubMed  CAS  Google Scholar 

  23. Heilmann C, Spanier C, Leberer E et al. Human liver calreticulin: characterization and Zn2+-dependent interaction with phenyl-sepharose. Biochem Biophys Res Commun 1993; 193:611–16.

    Article  PubMed  CAS  Google Scholar 

  24. Vassilakos A, Michalak M, Lehrman MA et al. Oligosaccharide binding characteristics of the molecular chaperones calnexin and calreticulin. Biochemistry 1998; 37:3480–90.

    Article  PubMed  CAS  Google Scholar 

  25. Corbett EF, Oikawa K, Francois P et al. Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J Biol Chem 1999; 274:6203–11.

    Article  PubMed  CAS  Google Scholar 

  26. Saito Y, Ihara Y, Leach MR et al. Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J 1999; 18:6718–29.

    Article  PubMed  CAS  Google Scholar 

  27. Corbett EF, Michalak KM, Oikawa K et al. The conformation of calreticulin is influenced by the endoplasmic reticulum lumenal environment. J Biol Chem 2000; 275:27177–85.

    PubMed  CAS  Google Scholar 

  28. Bouvier M, Stafford WF. Probing the three-dimensional structure of human calreticulin. Biochemistry 2000; 39:14950–59.

    Article  PubMed  CAS  Google Scholar 

  29. Li Z, Stafford WF, Bouvier M. The metal ion binding properties of calreticulin modulate its con-formational flexibility and thermal stability. Biochemistry 2001; 40:11193–201.

    Article  PubMed  CAS  Google Scholar 

  30. Michalak M, Corbett EF, Mesaeli N et al. Calreticulin: one protein, one gene, many functions. Biochem J 1999; 344:281–92.

    Article  PubMed  CAS  Google Scholar 

  31. Zuber C, Fan JY, Guhl B et al. Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates involvement of pre-Golgi intermediates in protein quality control. Proc Natl Acad Sci USA 2001; 98:10710–15.

    Article  PubMed  CAS  Google Scholar 

  32. Scott JE, Dawson JR. MHC class I expression and transport in a calnexin-deficient cell line. J Immunol 1995; 155:143–48.

    PubMed  CAS  Google Scholar 

  33. Nauseef WM, McCormick SJ, Clark RA. Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase. J Biol Chem 1995; 270:4741–47.

    Article  PubMed  CAS  Google Scholar 

  34. Ou WJ, Cameron PH, Thomas DY et al. Association of folding intermediates of glycoproteins with calnexin during protein maturation. Nature 1993; 364:771–76.

    Article  PubMed  CAS  Google Scholar 

  35. Ellgaard L, Molinari M, Helenius A. Setting the standards: quality control in the secretory pathway. Science 1999; 286:1882–88.

    Article  PubMed  CAS  Google Scholar 

  36. Bastianutto C, Clementi E, Codazzi F et al. Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol 1995; 130:847–55.

    Article  PubMed  CAS  Google Scholar 

  37. Mery L, Mesaeli N, Michalak M et al. Overexpression of calreticulin increases intracellular Ca2+ storage and decreases store-operated Ca2+ influx. J Biol Chem 1996; 271:9332–39.

    Article  PubMed  CAS  Google Scholar 

  38. Fasolato C, Pizzo P, Pozzan T. Delayed activation of the store-operated calcium current induced by calreticulin overexpression in RBL-1 cells. Mol Biol Cell 1998; 9:1513–22.

    PubMed  CAS  Google Scholar 

  39. Xu W, Longo FJ, Wintermantel MR et al. Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphophate-induced Ca2+ store depletion. J Biol Chem 2000; 275:36676–82.

    Article  PubMed  CAS  Google Scholar 

  40. Nakamura K, Zuppini A, Arnaudeau S et al. Functional specialization of calreticulin domains. J Cell Biol 2001; 154:961–72.

    Article  PubMed  CAS  Google Scholar 

  41. Camacho P, Lechleiter JD. Calreticulin inhibits repetitive intracellular Ca2+ waves. Cell 1995; 82(5):765–71.

    Article  PubMed  CAS  Google Scholar 

  42. John LM, Lechleiter JD, Camacho P. Differential modulation of SERCA2 isoforms by calreticulin. J Cell Biol 1998; 142:963–73.

    Article  PubMed  CAS  Google Scholar 

  43. Roderick HL, Lechleiter JD, Camacho P. Cytosolic phosphorylation of calnexin controls intracellular Ca2+ oscillations via an interaction with SERCA2b. J Cell Biol 2000; 149:1235–48.

    Article  PubMed  CAS  Google Scholar 

  44. McCauliffe DP, Lux FA, Lieu TS et al. Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen. J Clin Invest 1990; 85:1379–91.

    Article  PubMed  CAS  Google Scholar 

  45. Rokeach LA, Haselby JA, Meilof JF et al. Characterization of the autoantigen calreticulin. J Immunol 1991; 147:3031–39.

    PubMed  CAS  Google Scholar 

  46. Nakhasi HL, Pogue GP, Duncan RC et al. Implications of calreticulin function in parasite biology. Parasitol Today 1998; 14:157–60.

    Article  PubMed  CAS  Google Scholar 

  47. Kasper G, Brown A, Eberl M et al. A calreticulin-like molecule from the human hookworm Necator americanus interacts with Clq and the cytoplasmic signalling domains of some integrins. Parasite Immunol 2001; 23:141–52.

    Article  PubMed  CAS  Google Scholar 

  48. Lux FA, McCauliffe DP, Buttner DW et al. Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus. J Clin Invest 1992; 89:1945–51.

    Article  PubMed  CAS  Google Scholar 

  49. Meilof JF, Van der Lelij A, Rokeach LA et al. Autoimmunity and filariasis. Autoantibodies against cytoplasmic cellular proteins in sera of patients with onchocerciasis. J Immunol 1993; 151:5800–09.

    PubMed  CAS  Google Scholar 

  50. Pritchard DI, Brown A, Kasper G et al. A hookworm allergen which strongly resembles calreticulin. Parasite Immunol 1999; 21:439–50.

    Article  PubMed  CAS  Google Scholar 

  51. Sanders ML, Glass GE, Nadelman RB et al. Antibody levels to recombinant tick calreticulin increase in humans after exposure to Ixodes scapularis (Say) and are correlated with tick engorgement indices. Am J Epidemiol 1999; 149:777–84.

    Article  PubMed  CAS  Google Scholar 

  52. Eggleton P, Reid KB, Kishore U et al. Clinical relevance of calreticulin in systemic lupus erythematosus. Lupus 1997; 6:564–71.

    Article  PubMed  CAS  Google Scholar 

  53. Eggleton P, Llewellyn DH. Pathophysiological roles of calreticulin in autoimmune disease. Scand J Immunol 1999; 49:466–73.

    Article  PubMed  CAS  Google Scholar 

  54. Botto M. Clq knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 1998; 15:231–34.

    Article  PubMed  CAS  Google Scholar 

  55. Nash JT, Taylor PR, Botto M et al. Immune complex processing in Clq-deficient mice. Clin Exp Immunol 2001; 123:196–202.

    Article  PubMed  CAS  Google Scholar 

  56. Lewis JW, Elliott T. Evidence for successive peptide binding and quality control stages during MHC class I assembly. Curr Biol 1998; 8:717–20.

    Article  PubMed  CAS  Google Scholar 

  57. Goicoechea S, Orr AW, Pallero MA et al. Thrombospondin mediates focal adhesion disassembly through interactions with cell surface calreticulin. J Biol Chem 2000; 275:36358–68.

    Article  PubMed  CAS  Google Scholar 

  58. Guo L, Lynch J, Nakamura K et al. COUP-TFl antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development. J Biol Chem 2001; 276:2797–801.

    Article  PubMed  CAS  Google Scholar 

  59. Nakamura K, Robertson M, Liu G et al. Complete heart block and sudden death in mouse over-expressing calreticulin. J Clin Invest 2001; 107:1245–53.

    Article  PubMed  CAS  Google Scholar 

  60. Zhu N, Pewitt EB, Cai XY et al. Calreticulin: An intracellular Ca2+-binding protein abundantly expressed and regulated by androgen in prostatic epithelial cells. Endocrinology 1998; 139:4337–44.

    Article  PubMed  CAS  Google Scholar 

  61. Zhu N, Wang Z. Calreticulin expression is associated with androgen regulation of the sensitivity to calcium ionophore-induced apoptosis in LNCaP prostate cancer cells. Cancer Res 1999; 59:1896–902.

    PubMed  CAS  Google Scholar 

  62. Foyouzi-Youseffi R, Arnaudeau S, Borner C et al. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc Natl Acad Sci USA 2000; 97:5723–28.

    Article  Google Scholar 

  63. Pinton P, Ferrari D, Magalhaes P et al. Reduced loading of intracellular Ca2+ stores and downregulation of capacitative Ca2+ influx in Bcl-2-overexpressing cells. J Cell Biol 2000; 148:857–62.

    Article  PubMed  CAS  Google Scholar 

  64. Nakamura K, Bossy-Wetzel E, Burns K et al. Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis. J Cell Biol 2000; 150:731–40.

    Article  PubMed  CAS  Google Scholar 

  65. Bruchovsky N, Snoek R, Rennie PS et al. Control of tumor progression by maintenance of apoptosis. Prostate 1996; 6:13–21.

    Article  PubMed  CAS  Google Scholar 

  66. Bleackley RC, Atkinson EA, Burns K et al. Calreticulin: a granule-protein by default or design? Curr Topics Microbiol Immunol 1995; 198:145–59.

    Article  CAS  Google Scholar 

  67. Ogden CA, deCathelineau A, Hoffmann PR et al. Clq and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001; 194:781–95.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Paul Eggleton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marek Michalak
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Peninsula Medical School, Devon, U.K. MRC Immunochemistry Unit Department of Biochemistry, University of Oxford, Oxford, UK

    Paul Eggleton Ph.D.

  2. CIHR Membrane Protein Research Group Department of Biochemistry, University of Alberta Edmonton, Alberta, Canada

    Marek Michalak Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Eggleton, P., Michalak, M. (2003). Introduction to Calreticulin. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9258-1_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4862-7

  • Online ISBN: 978-1-4419-9258-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation